The preparation of ternary mixtures of a particulate carrier, a first particulate inhalant medicament and a second particulate inhalant medicament poses particular problems when one medicament is present at a relatively small proportion compared to the other medicament. It is difficult to prepare mixtures which are homogeneous. In addition, small quantities of medicament may sometimes bind to the inert carrier, which can affect the amount of medicament that is made available to the patient when the formulation is delivered, e.g. by means of a dry powder inhaler (DPI) device. In such devices, a metered dose of composition comprising one or more active ingredients and an inert carrier, such as lactose, is dispensed into the air stream that is produced by the inspirational effort of the patient. The medicaments and carrier are entrained in this air stream, with only the fine particles of medicament entering the deep recesses of the lung (which is the site of action of the medicament), the inert excipient being deposited either in the mouth or in the upper region of the lungs.
The accurate metering of highly potent inhalant drugs causes particular problems, as the quantity of medicament in the composition relative to that of the carrier is often particularly small (less than 1 part of drug to 50 parts of carrier). This is exemplified by the medicament formoterol, which is often administered to patients at a dose of less than 60 micrograms (doses may be as small as 6 micrograms).
Thus, methods of producing ternary mixtures that are homogeneous and can be used with suitable dry powder inhalers, to give dose uniformity, reliability, and uniform dispersion of a plurality of medicaments in the composition are needed.